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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q14145: Variant p.Gly430Cys

Kelch-like ECH-associated protein 1
Gene: KEAP1
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Variant information Variant position: help 430 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help US The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change: help From Glycine (G) to Cysteine (C) at position 430 (G430C, p.Gly430Cys). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: help Change from glycine (G) to medium size and polar (C) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -3 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Variant description: help In a lung adenocarcinoma patient; somatic mutation; strongly reduces interaction with NFE2L2/NRF2 and reduces repression of NFE2L2/NRF2-dependent gene expression. Any additional useful information about the variant.


Sequence information Variant position: help 430 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 624 The length of the canonical sequence.
Location on the sequence: help SVPRNRIGVGVIDGHIYAVG G SHGCIHHNSVERYEPERDEW The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: help The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human                         SVPRNRIGVGVIDGHIYAVGGSHGCIHHNSVERYEPERDEW

Mouse                         SVPRNRIGVGVIDGHIYAVGGSHGCIHHSSVERYEPERDEW

Rat                           SVPRNRSGGGVIDGHIYAVGGSHGCIHHSSVERYEPDRDEW

Pig                           SVPRNRIGVGVIDGHIYAVGGSHGCIHHNSVERYEPERDEW

Sequence annotation in neighborhood: help The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.
TypePositionsDescription
Chain 1 – 624 Kelch-like ECH-associated protein 1
Repeat 424 – 470 Kelch 3
Site 434 – 434 Sensor for electrophilic agents
Modified residue 434 – 434 S-cGMP-cysteine
Mutagenesis 415 – 415 R -> A. Loss of interaction with NFE2L2/NRF2. Abolishes repression of NFE2L2/NRF2-dependent gene expression. Loss of interaction with PGAM5. Does not affect interaction with SQSTM1/p62.
Mutagenesis 436 – 436 H -> A. Loss of interaction with NFE2L2/NRF2. Abolishes repression of NFE2L2/NRF2-dependent gene expression. Does not affect interaction with SQSTM1/p62.



Literature citations
Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer.
Padmanabhan B.; Tong K.I.; Ohta T.; Nakamura Y.; Scharlock M.; Ohtsuji M.; Kang M.; Kobayashi A.; Yokoyama S.; Yamamoto M.;
Mol. Cell 21:689-700(2006)
Cited for: VARIANTS CYS-364 AND CYS-430; CHARACTERIZATION OF VARIANTS CYS-364 AND CYS-430;
Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.